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Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers.

Publication ,  Journal Article
Schorcht, A; van den Kerkhof, TLGM; Cottrell, CA; Allen, JD; Torres, JL; Behrens, A-J; Schermer, EE; Burger, JA; de Taeye, SW; Bontjer, I ...
Published in: J Virol
November 23, 2020

The induction of broadly neutralizing antibodies (bNAbs) is a major goal in vaccine research. HIV-1-infected individuals that develop exceptionally strong bNAb responses, termed elite neutralizers, can inform vaccine design by providing blueprints for the induction of similar bNAb responses. We describe a new recombinant native-like envelope glycoprotein (Env) SOSIP trimer, termed AMC009, based on the viral founder sequences of an elite neutralizer. The subtype B AMC009 SOSIP protein formed stable native-like trimers that displayed multiple bNAb epitopes. Overall, its structure at 4.3-Å resolution was similar to that of BG505 SOSIP.664. The AMC009 trimer resembled one from a second elite neutralizer, AMC011, in having a dense and complete glycan shield. When tested as immunogens in rabbits, the AMC009 trimers did not induce autologous neutralizing antibody (NAb) responses efficiently while the AMC011 trimers did so very weakly, outcomes that may reflect the completeness of their glycan shields. The AMC011 trimer induced antibodies that occasionally cross-neutralized heterologous tier 2 viruses, sometimes at high titer. Cross-neutralizing antibodies were more frequently elicited by a trivalent combination of AMC008, AMC009, and AMC011 trimers, all derived from subtype B viruses. Each of these three individual trimers could deplete the NAb activity from the rabbit sera. Mapping the polyclonal sera by electron microscopy revealed that antibodies of multiple specificities could bind to sites on both autologous and heterologous trimers. These results advance our understanding of how to use Env trimers in multivalent vaccination regimens and the immunogenicity of trimers derived from elite neutralizers.IMPORTANCE Elite neutralizers, i.e., individuals who developed unusually broad and potent neutralizing antibody responses, might serve as blueprints for HIV-1 vaccine design. Here, we studied the immunogenicity of native-like recombinant envelope glycoprotein (Env) trimers based on viral sequences from elite neutralizers. While immunization with single trimers from elite neutralization did not recapitulate the breadth and potency of neutralization observed in these infected individuals, a combination of three subtype B Env trimers from elite neutralizers resulted in some neutralization breadth within subtype B viruses. These results should guide future efforts to design vaccines to induce broadly neutralizing antibodies.

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

November 23, 2020

Volume

94

Issue

24

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Recombinant Proteins
  • Rabbits
  • Immunization
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • Glycoproteins
  • Epitopes
 

Citation

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Schorcht, A., van den Kerkhof, T. L. G. M., Cottrell, C. A., Allen, J. D., Torres, J. L., Behrens, A.-J., … Sanders, R. W. (2020). Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J Virol, 94(24). https://doi.org/10.1128/JVI.01214-20
Schorcht, Anna, Tom L. G. M. van den Kerkhof, Christopher A. Cottrell, Joel D. Allen, Jonathan L. Torres, Anna-Janina Behrens, Edith E. Schermer, et al. “Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers.J Virol 94, no. 24 (November 23, 2020). https://doi.org/10.1128/JVI.01214-20.
Schorcht A, van den Kerkhof TLGM, Cottrell CA, Allen JD, Torres JL, Behrens A-J, et al. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J Virol. 2020 Nov 23;94(24).
Schorcht, Anna, et al. “Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers.J Virol, vol. 94, no. 24, Nov. 2020. Pubmed, doi:10.1128/JVI.01214-20.
Schorcht A, van den Kerkhof TLGM, Cottrell CA, Allen JD, Torres JL, Behrens A-J, Schermer EE, Burger JA, de Taeye SW, Torrents de la Peña A, Bontjer I, Gumbs S, Ozorowski G, LaBranche CC, de Val N, Yasmeen A, Klasse PJ, Montefiori DC, Moore JP, Schuitemaker H, Crispin M, van Gils MJ, Ward AB, Sanders RW. Neutralizing Antibody Responses Induced by HIV-1 Envelope Glycoprotein SOSIP Trimers Derived from Elite Neutralizers. J Virol. 2020 Nov 23;94(24).

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

November 23, 2020

Volume

94

Issue

24

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Virology
  • Recombinant Proteins
  • Rabbits
  • Immunization
  • HIV-1
  • HIV Infections
  • HIV Antibodies
  • Glycoproteins
  • Epitopes